Published online before print February 23, 2009

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(Journal of Leukocyte Biology. 2009;85:896-903.)
© 2009 Society for Leukocyte Biology

Defective IL-10 production in severe phenotypes of Crohn’s disease

Ismael Correa^*, Marisol Veny, Miriam Esteller, Josep M. Piqué^*, Jordi Yagüe, Julián Panés^* and Azucena Salas^,1

^* Departments of Gastroenterology and
Immunology, Hospital Clínic, IDIBAPS, and
Department of Experimental Pathology, Institut d’Investigaciones Biomèdiques de Barcelona (IIBB)-Consejo Superior de Investigaciones Científicas, CIBER-EHD, Barcelona, Spain

¹ Correspondence: Department of Experimental Pathology, Institut d’Investigaciones Biomèdiques de Barcelona (IIBB)-CSIC, Rosselló 161, Barcelona 08036, Spain. E-mail: azsbam{at}iibb.csic.es

ABSTRACT

Loss of tolerance toward commensal bacteria has been invoked as a mechanism for Crohn’s disease. IL-10 is a key anti-inflammatory cytokine that plays a role in induction and maintenance of tolerance. The aim of this study is to determine IL-10 production in response to bacterial components in Crohn’s disease patients, who were classified according to their phenotypes as stricturing, penetrating, or inflammatory. Peripheral blood was obtained from Crohn’s disease patients and healthy controls. Cytokine production was measured in whole blood cultures, isolated CD4⁺ cells, and monocyte-derived dendritic cells (MDDCs). Under unstimulated conditions, IL-10, but not IL-12, was down-regulated significantly in blood cultures of patients with severe phenotypes, compared with inflammatory, nonpenetrating, nonstricturing Crohn’s disease patients. In response to LPS, IL-10 was up-regulated more significantly in patients with no fistulae or fibrosis. Study of IL-10 production by isolated cell subsets showed that DCs, but not CD4⁺ T cells, from penetrating Crohn’s disease produced significantly less IL-10 in response to LPS. Differences were not associated with the 1082A/G polymorphism in the IL-10 gene promoter. We show a defect in IL-10 production in whole blood cell cultures and MDDCs in patients with severe forms of Crohn’s disease. This defect in IL-10 production by a group of Crohn’s disease patients may represent a mechanism mediating more severe manifestations of the disease. We propose that treatment with IL-10 or IL-10-inducing therapies could be of particular benefit to these group of patients.

Key Words: dendritic cell • IL-12 • dendritic cell • LPS